Lactic acid bacteria are increasingly becoming important as hosts for recombinant expression of heterologous polypeptides in vitro (e.g., U.S. Pat. No. 5,559,007) as well as for in vivo or in situ expression and delivery of antigens and/or therapeutically relevant polypeptides (e.g., WO 97/14806).
Lactic acid bacteria, and particularly Lactococcus, are considered as GRAS-microorganisms (i.e., regarded as generally safe) and may thus be relatively readily administered to humans and animals.
However, achieving strong level of heterologous expression in lactic acid bacteria often requires the introduction of promoters and other sequences that are exogenous to these bacteria (e.g., see Wells et al., 1993A) and therefore may compromise the GRAS perception thereof.
Accordingly, there exists a need to provide further promoters which are derived from lactic acid bacteria, more preferably from Lactococcus, and can be favourably used for expression of proteins, preferably heterologous protein expression, therein.
Also needed are such promoters which can achieve high expression levels in order to obtain sufficient amounts of so-expressed proteins in industrial and/or therapeutic settings.